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Bone

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Cardiovasculature

Cardiomyocytes and fibroblasts

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FLEXCELL® INTERNATIONAL CORPORATION

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96. Fujioka K'' Azuma N'' Kito H'' Gahtan V'' Esato K'' Sumpio BE. Role of caveolin in hemodynamic force-mediated endothelial changes. J Surg Res 92(1):7-10'' 2000.

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101. Hishikawa K'' Luscher TF. Pulsatile stretch stimulates superoxide production in human aortic endothelial cells. Circulation 96(10):3610-3616'' 1997.

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106. Iba T'' Sumpio BE. Morphological response of human endothelial cells subjected to cyclic strain in vitro. Microvasc Res 42(3):245-254'' 1991.

107. Ikeda M'' Kito H'' Sumpio BE. Phosphatidylinositol-3 kinase dependent MAP kinase activation via p21ras in endothelial cells exposed to cyclic strain. Biochem Biophys Res Commun 257(3):668-671'' 1999.

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117. Lee T'' Kim SJ'' Sumpio BE. Role of PP2A in the regulation of p38 MAPK activation in bovine aortic endothelial cells exposed to cyclic strain. J Cell Physiol 194(3):349-355'' 2003.

118. Li W'' Sumpio BE. Strain-induced vascular endothelial cell proliferation requires PI3K-dependent mTOR-4E-BP1 signal pathway. Am J Physiol Heart Circ Physiol 288(4):H1591-1597'' 2005.

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131. Segurola RJ Jr'' Oluwole B'' Mills I'' Yokoyama C'' Tanabe T'' Kito H'' Nakajima N'' Sumpio BE. Cyclic strain is a weak inducer of prostacyclin synthase expression in bovine aortic endothelial cells. J Surg Res 69(1):135-138'' 1997.

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133. Sumpio BE'' Banes AJ'' Levin LG'' Johnson G Jr. Mechanical stress stimulates aortic endothelial cells to proliferate. J Vasc Surg 6(3):252-256'' 1987.

134. Sumpio BE'' Banes AJ'' Link GW'' Iba T. Modulation of endothelial cell phenotype by cyclic stretch: inhibition of collagen production. J Surg Res 48(5):415-420'' 1990.

135. Sumpio BE'' Banes AJ. Prostacyclin synthetic activity in cultured aortic endothelial cells undergoing cyclic mechanical deformation. Surgery 104(2):383-389'' 1988.

136. Sumpio BE'' Chang R'' Xu WJ'' Wang XJ'' Du W. Regulation of tPA in endothelial cells exposed to cyclic strain: role of CRE'' AP-2'' and SSRE binding sites. Am J Physiol Cell Physiol 273:C1441-C1448'' 1997.

137. Sumpio BE'' Du W'' Galagher G'' Wang X'' Khachigian LM'' Collins T'' Gimbrone MA Jr'' Resnick N. Regulation of PDGF-B in endothelial cells exposed to cyclic strain. Arterioscler Thromb Vasc Biol 18(3):349-355'' 1998.

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147. von Offenberg Sweeney'' Cummins PM'' Cotter EJ'' Fitzpatrick PA'' Birney YA'' Redmond EM'' Cahill PA. Cyclic strain-mediated regulation of vascular endothelial cell migration and tube formation. Biochemical and Biophysical Research Communications 329:573–582'' 2005.

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150. Wang DL'' Wung BS'' Shyy YJ'' Lin CF'' Chao YJ'' Usami S'' Chien S. Mechanical strain induces monocyte chemotactic protein-1 gene expression in endothelial cells. Effects of mechanical strain on monocyte adhesion to endothelial cells. Circ Res 77(2):294-302'' 1995.

151. Widmann MD'' Letsou GV'' Phan S'' Baldwin JC'' Sumpio BE. Isolation and characterization of rabbit cardiac endothelial cells: Response to cyclic strain and growth factors in vitro. Journal of Surgical Research 53(4):331-334'' 1992.

152. Wilson CJ'' Kasper G'' Schütz MA'' Duda GN. Cyclic strain disrupts endothelial network formation on Matrigel. Microvasc Res 78(3):358-63'' 2009. Epub 2009 Aug 18.

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157. Wung BS'' Cheng JJ'' Hsieh HJ'' Shyy YJ'' Wang DL. Cyclic strain-induced monocyte chemotactic protein-1 gene expression in endothelial cells involves reactive oxygen species activation of activator protein 1. Circ Res 81(1):1-7'' 1997.

158. Wung BS'' Cheng JJ'' Shyue SK'' Wang DL. NO modulates monocyte chemotactic protein-1 expression in endothelial cells under cyclic strain. Arterioscler Thromb Vasc Biol 21(12):1941-1947'' 2001.

159. Yamaguchi S'' Yamaguchi M'' Yatsuyanagi E'' Yun SS'' Nakajima N'' Madri JA'' Sumpio BE. Cyclic strain stimulates early growth response gene product 1-mediated expression of membrane type 1 matrix metalloproteinase in endothelium. Lab Invest 82(7):949-956'' 2002.

160. Yano Y'' Geibel J'' Sumpio BE. Cyclic strain induces reorganization of integrin α5β1 and α2β1 in human umbilical vein endothelial cells. J Cell Biochem 64(3):505-513'' 1997.

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161. Yano Y'' Geibel J'' Sumpio BE. Tyrosine phosphorylation of pp125FAK and paxillin in aortic endothelial cells induced by mechanical strain. Am J Physiol Cell Physiol 271:C635-C649'' 1996.

162. Yano Y'' Saito Y'' Narumiya S'' Sumpio BE. Involvement of rho p21 in cyclic strain-induced tyrosine phosphorylation of focal adhesion kinase (pp125FAK)'' morphological changes and migration of endothelial cells. Biochem Biophys Res Commun 224(2):508-515'' 1996.

163. Zheng W'' Christensen LP'' Tomanek RJ. Stretch induces upregulation of key tyrosine kinase receptors in microvascular endothelial cells. Am J Physiol Heart Circ Physiol 287(6):H2739-H2745'' 2004.

164. Zheng W'' Seftor EA'' Meininger CJ'' Hendrix MJ'' Tomanek RJ. Mechanisms of coronary angiogenesis in response to stretch: role of VEGF and TGF-β. Am J Physiol Heart Circ Physiol 280(2):H909-H917'' 2001.

165. Zheng W'' Christensen LP'' Tomanek RJ. Differential effects of cyclic and static stretch on coronary microvascular endothelial cell receptors and vasculogenic/angiogenic responses. Am J Physiol Heart Circ Physiol 295:H794–H800'' 2008.

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167. Birukov KG'' Shirinsky VP'' Stepanova OV'' Tkachuk VA'' Hahn AW'' Resink TJ'' Smirnov VN. Stretch affects phenotype and proliferation of vascular smooth muscle cells. Mol Cell Biochem 144(2):131-139'' 1995.

168. Capers Q 4th'' Alexander RW'' Lou P'' De Leon H'' Wilcox JN'' Ishizaka N'' Howard AB'' Taylor WR. Monocyte chemoattractant protein-1 expression in aortic tissues of hypertensive rats. Hypertension 30(6):1397-1402'' 1997.

169. Cattaruzza M'' Berger MM'' Ochs M'' Fayyazi A'' Fuzesi L'' Richter J'' Hecker M. Deformation-induced endothelin B receptor-mediated smooth muscle cell apoptosis is matrix-dependent. Cell Death Differ 9(2):219-226'' 2002.

170. Cattaruzza M'' Dimigen C'' Ehrenreich H'' Hecker M. Stretch-induced endothelin B receptor-mediated apoptosis in vascular smooth muscle cells. FASEB J 14(7):991-998'' 2000.

171. Chang H'' Shyu KG'' Wang BW'' Kuan P. Regulation of hypoxia-inducible factor-1α by cyclical mechanical stretch in rat vascular smooth muscle cells. Clin Sci (Lond) 105(4):447-456'' 2003.

172. Chapman GB'' Durante W'' Hellums JD'' Schafer AI. Physiological cyclic stretch causes cell cycle arrest in cultured vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 278:H748-H754'' 2000.

173. Chen AH'' Gortler DS'' Kilaru S'' Araim O'' Frangos SG'' Sumpio BE. Cyclic strain activates the pro-survival Akt protein kinase in bovine aortic smooth muscle cells. Surgery 130(2):378-381'' 2001.

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美国Flexcellint国际公司，成立于1987年，该公司专注于细胞力学培养产品的设计和制造。以提供独特的体外细胞拉应力、压应力和流体剪切应力加载刺激系统以及配套的培养板、硅胶膜载片等耗材闻名于世。

Flexcell的细胞组织体外机械力加载装置的细胞力学加载方法和能模拟生命体内细胞组织生长生物力环境、实现体外分离和建立合适的加载膜型公认国际领先''详见应用案例文献库

Flexcell细胞组织力学培养系统不仅能对各种2D、3D细胞组织提供拉应力、压应力、切应力刺激加载，而且还可以提供拉应力和切应力混合力同时加载；不仅能对细胞组织进行机械力加载刺激，而且还能三维培养、人工生物组织构建、动力模拟；不仅能单轴向牵张拉伸，而且还可以双轴向牵张拉伸。

Flexcell独具的StageFlexer拉应力显微设备、StagePresser压应力显微设备、Flex Flow切应力显微设备；这些显微设备可在加力培养的同时实时观察研究细胞组织反应变化；独具的flexstop隔离阀能使同一块培养板里的细胞组织一部分受力，一部分不受力，方便进行对比实验

这些系统智能、精准诱导来自各种细胞、组织在拉力、压力和流体切应力作用下发生的生化生理变化，专业、细腻的阐释了体外细胞、组织机械力刺激加载、力学信号感受和响应机制。对研究细胞的形态结构及功能，细胞的生长、发育、成熟、增殖、衰老、凋亡、死亡及癌变以及通路表达，细胞信号传导及基因表达的调控，细胞的分化及其调控机理具有重要意义。

典型应用科室:

口腔	颞下颌关节滑膜细胞、人牙周膜细胞、口腔上皮细胞、口腔鳞癌KB细胞等
骨:	骨骼细胞、肌腱细胞、韧带细胞、软骨细胞和骨细胞、骨髓间充质干细胞，软骨组织、椎间盘骨组织、肌腱组织、韧带组织等
肺呼吸	肺细胞、肺上皮细胞、肺动脉内皮细胞、人肺微血管内皮细胞
眼科视觉神经	眼上皮细胞、眼小梁组织细胞、视网膜神经细胞
心血管/高血压:	心肌细胞、血细胞、心血管平滑肌细胞、血管内皮细胞
生殖	肾膀胱细胞、平滑肌细胞/尿路上皮及尿路上皮细胞、肾小管上皮细胞
消化	肠上皮细胞、胃上皮细胞、胃血管内皮细胞
皮肤	皮肤细胞、皮肤成纤维细胞
Flexcell模块化的拉应力、压应力、切应力、三维培养模块，可任意组合统一主机多功能平台

1、FX-5000T细胞牵张拉伸应力加载系统(Flexcell FX5000 Tension system)

1）该系统对二维、三维细胞和组织提供轴向和圆周应力加载；
2）基于柔性膜基底变形、受力均匀;
3）可实时观察细胞、组织在应力作用下的反应;
4）独具的flexstop隔离阀可使同一块培养板力的一部分培养孔的细胞受力，一部分培养孔的细胞不受力，方便对比实验;
5）与压力传导仪整合，同时兼备多通道细胞压力加载功能;
6）与Flex Flow平行板流室配套，可在牵拉细胞的同时施加流体切应力;
7）多达4通道，可4个不同程序同时运行，进行多个不同拉伸形变率对比实验；
8）同一程序中可以运行多种频率，多种振幅和多种波形；
9）更好地控制在超低或超高应力下的波形；
10）多种波形种类：静态波形、正旋波形、心动波形、三角波形、矩形以及各种特制波形；
11)电脑系统对牵张拉伸力加载周期、大小、频率、持续时间精确智能调控
12)加载分析各种细胞在牵张拉应力刺激下的生物化学反应
13)伸展度：0-33%
14)牵拉频率：0.01-5Hz

2、FX-5000C细胞压力加载系统(flexcell FX5000 Compression system)——提供样机体验

1）该系统对各种组织、三维细胞培养物提供周期性或静态的压力加载；
2）基于柔性膜基底变形、受力均匀;
3）可实时观察细胞、组织在压力作用下的反应;
4）可有选择性地封阻对细胞的应力加载;

5）同时兼备多通道细胞牵拉力加载功能;

6）多达4通道，可4个不同程序同时运行，进行多个不同压力形变率对比实验；

7）同一程序中可以运行多种频率(0.01- 5 Hz)，多种振幅和多种波形；
8）更好地控制在超低或超高应力下的波形；
9）多种波形种类：静态波形、正旋波形、心动波形、三角波形、矩形以及各种特制波形；
10)电脑系统对压力加载周期、大小、频率、持续时间精确智能调控
11)检测各种组织和细胞在压力作用下的生物化学反应
12)压力范围：0.1 - 14磅

3、TissueTrain可拉伸组织工程三维细胞培养系统(Flexcell TissueTrain System)——提供样机体验

FLEXCELL Tissue Train® 是个独立的全自动细胞组织三维培养、组织构建计算机智能控制的生物反应器系统，它允许研究者创建三维基质凝胶支架，

在基质里细胞培养、构建生物组织，可为三维细胞、组织提供双轴向应力和单轴向应力，FLEXCELL Tissue Train®

是当今科研界最先进的可拉伸刺激三维细胞培养、生物组织构建系统系统。

系统功能亮点：

三维细胞牵张应力加载刺激：对生长在三维状态下的细胞进行静态的或者周期性的拉应力刺激
通过Flexcell应力加载系统和弧矩形加载平台对生长在三维环境下的细胞进行单轴向
或者双轴向的静态或者周期性的应力加载刺激培养
三维细胞培养：使用三维组织培养模具和三维细胞培养板可以进行三维细胞培养在凝胶支架里全自动三维培养
三维组织培养模具和三维细胞培养板类型丰富：
1)三维组织培养模具有三维线形培养加载基站模具和三维梯形培养加载基站模具
2)具有氨基酸包被表面、胶原（I型或IV）包被表面、弹性蛋白包被表面、ProNectin（RGD）包被表面、层粘连蛋白（YIGSR）包被表面的三维培养板。
科研者根据自己的细胞，有针对性的选择适合包被表面三维培养板
3)具有可牵拉双轴向和单轴向拉力刺激加载三维组织培养板。
大体积三维生物人工组织培养构建：可构建长度达35mm的生物人工组织
动力模拟实验:可建立特制的各种模拟实验：心率模拟实验、步行模拟实验、跑动模拟实验和其他动力模拟实验
本系统技术先进性：
1）安全快速的扩增细胞
2）在细胞特异性基质(圆盘形陶瓷载体培养片) 中进行三维的细胞高密度培养
3）扩增并获得可用于治疗的有活性的原代细胞
4）在控制分化状态的条件下扩增干细胞
5）向植入的一代细胞提供植入支架
6）长期培养分泌细胞
7）高效生产重组蛋白和疫苗
8）生产优质的糖蛋白
9）三维培养与机械力刺激有机结合
10）三维凝胶压实自动测量与面积自动计算
可用于多个领域，如研究、生物制药加工；也可为细胞和组织培养工作提供解决方案：
1）可用于干细胞和胚体扩增及定向分化
2）可用于细胞和组织治疗的细胞制备
3）可用于克隆细胞，为器官移植做准备（例如hip stem'' heart valve'' graft）
4）可用于制备天然的生物制品（例如糖蛋白、病毒、病毒样颗粒）
观察细胞应力下实时反映：使用Flexcell独有的Flexcell StageFlexer Jr.显微附属设备，可在加力刺激的同时实时观察细胞在三维状态下牵拉刺激的反应
多种基质蛋白包被的尼龙网锚可以加强细胞与网锚的结合

4、STR-4000细胞流体切应力系统(Flexcell Fluid Shear Stress Device)——提供样机体验

4.1、六通道流体切应力加载分析设备—Streamer剪切力设备

为细胞提供各种形式的流体切应力：稳流式切应力、脉冲式切应力或者往返式切应力。
在经过特殊基质蛋白包被的25x 75x 1.0mm细胞培养载片上培养细胞。
多达6通道，每个通道放不同载片，可培养不同的细胞
计算机控制的蠕动泵可以调节切应力大小从0-35 dynes/cm²
通过Osci-Flow液体控制仪提供往返式或脉冲式流体切应力。
检测细胞在液流作用下的排列反应。
设备易拆卸并可高温消毒。
可以在经过特殊包被的6个细胞培养载片上同时培养细胞。
提供两个液流脉冲阻尼器。
Streamer System产品包括：
1)Streamer设备；
2) DELL笔记本式计算机；
3)快拆接头及胶管；
4)蠕动泵；
5）StreamSoft软件；
6）2个液流脉冲阻尼器；
7）12个细胞培养载片(Culture Slip)
4.2、HiQ Flowmate纳升和微微液流控制双注射系统
双注射泵可以在微升，纳升和微微升水平上控制液流.双注射泵，独立的液流控制系统。
传送精确，稳定的流速
可控流速范围1.2pL/ min-260.6ml/min
提供不同流速模型：稳定型，脉冲型，连续型，截流型和震荡型；
可进行循环，连续的液流控制；同时运行不同的流速模型；
内置阀门控制液流模式；
机载计算器用于流量、流时、流速、剪切力的计算；
高分辨率、触屏控制。
用户友好的图标驱动程序；
便于泵和芯片对接的生物芯片支架；根据现有流速有三种不同的机型；
多种应用程序：
液体稀释，配给及注射器；
动物实验中的药物注射和体液抽取；
施加液流剪切力；
微流体和纳流体实验；
混合、分流液体；
震荡型液流的控制需要iHIQ Flowmate二级阀门配件

4.3 Osci-Flow切应力模式控制器——完美的液流控制模式
通过计算机控制提供可调控的，往返式的或者脉冲式的流体切应力。
和Streamer及FlexFlow shear stress设备一起使用。
维持泵的流速不''最大限度的降低改变泵的转速引起的流液的延反应迟。
可以在瞬间内改变流体流动方向。
兼容其它公司生产的灌流系统。
兼容各种类型MasterFlexL/S系列或者相应的胶管。
通过PC板卡可以和绝大多数便携式计算机连接使用。
Osci-Flow装置DAQ Card DIO-24说明书和NI-DAQ软件
连接Osci-Flow和板卡的缆线;
DELL电脑需单独购买
胶管和快拆接头;StreamSoft软件;

5、Flexflow平行板流室系统提供流体切应力同时抻拉细胞

FlexcellFlexFlow显微切应力加载设备（SHEAR Stress device）

可以在提供流体切应力的同时抻拉细胞，测试血管和结绨组织细胞对液体流动的实时反应。
为培育在StageFlexer硅胶模表面或者基质蛋白包被的细胞培养片上的细胞提供切应力。
使用FX-5000T应力加载系统抻拉细胞，并且可以在实验前，实验中或者实验后提供切应力。
计算机控制蠕动泵，调节切应力大小，从0-35 dynes/cm²
使用标准正立式显微镜实时观察细胞在切应力下的反应。
检测细胞在流体作用下的排列反应。
检测在液体切应力下各种激活剂/抑制剂对细胞反应的影响。使用荧光团例如FURA-2检测细胞内[Ca2+]ic或者其它离子对切应力反应。
FlexFlow系统包括：
FlexFlow装置；StreamSoft软件
FlexFlow快拆接头、胶管、FlexFlow 旁路连接器
MASTERFLEX L/S型号7550-10蠕动泵及配套线缆、连接管
2个稳流器；硅润滑剂
FX -5000 张力系统适配器
显微镜适应性FlexFlow底座
快速链接细胞培养基瓶；一个快速链接真空瓶
三个没灭菌和六个灭菌胶原蛋白涂层薄培养载片
三个没灭菌和六个灭菌胶原涂层StageFlexer膜
配件包
保证细胞在不同水平恒流或生理剪切力作用下仍保持黏附，在研究中得到了广泛应用。用蠕动泵（peristaltic pump）或注射泵（syringe pump）提供瞬态剪切力使平行板流室的入流管和出流管之间产生压差，使流室内细胞受到均匀，震荡或脉动剪切力的作用。

平台总结：
- 力类型：具有细胞组织力学所要求的所有类型：牵张拉伸力、压力、流体切应力（各种形式的流体切应力：稳流式切应力，脉冲式切应力或者往返式切应力）
- 轴向：不但具有双轴向拉伸力加载，还具备单轴向加力功能
- 培养物类型：能对各种2D和3D细胞级别或组织级别培养加载刺激；可以构建长达35mm的人工生物组织
- 压应力和拉应力波形类型：波形丰富''既能提供模拟加载的静态波形、正旋波形、心动波形、三角波形、矩形波形和各种自定义波形
- 平台扩充性：在同一电脑主机上，具备拉应力、压应力、流体切应力模块任意组合
- 系统压力可扩展性：具有模块化、多通道加载功能，可进行不同压缩形变对比实验室
- 系统牵张拉伸力可扩展性：具有模块化、多通道加载功能，可进行不同牵张拉伸形变对比实验室
- 系统切应力可扩展性：流体切应力模块和拉应力可同时混合加载刺激
- 产品成熟度：国外内有大量应用文献案例（详见应用案例文献库），国内至少有10家成功使用案例

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4.1、六通道流体切应力加载分析设备—Streamer剪切力设备

4.2、HiQ Flowmate纳升和微微液流控制双注射系统

4.3 Osci-Flow切应力模式控制器——完美的液流控制模式